Method and Apparatus for removing senescent cells

Abstract

A major type of unwanted cells that accumulate in aging are anergic cytotoxic T-cells. These cells often have virus-specific T-cell receptors, as well as other surface markers that distinguish them from their youthful counterparts, and are thought to play a major role in the decline of the immune system with age. Here we disclose the use of magnetic cell separation methods and apparatuses to remove senescent T-cells defined by the surface markers CD8+, KLRG1+ and CD8+, CD28−. We disclose how these markers are used to remove anergic T-cells from the blood of aged C57BL/6 mice, resulting in lasting rejuvenation of their immunological marker profile. Using antibodies with magnetic microparticles linked to their Fc domains, we first developed a method to use magnets to filter out the unwanted cells from the blood, and later constructed a device that does this automatically.

1 . A method of removing senescent cells substantially from a patient's body using apparatus as described herein, in order to improve immune system function in aging. 
     
     
         2 . The method of  claim 1 , where the senescent cells are defined by CD8+, CD28−. 
     
     
         3 . The method of  claim 1 , where the senescent cells are defined by CD8+, KLRG1+. 
     
     
         4 . The method of  claim 1 , where the senescent cells are defined by CD8+, CD57+. 
     
     
         5 . The method of  claim 1 , where the senescent cells are defined by KLRG1+. 
     
     
         6 . The method of  claim 1 , where patient is elderly. 
     
     
         7 . The method of  claim 1 , where the patient needs a vaccine in the near future. 
     
     
         8 . The method of  claim 1 , where the patient is at risk of viral infection. 
     
     
         9 . The method of  claim 1 , where the patient is Cytomegalovirus positive. 
     
     
         10 . The method of  claim 1 , where the patient is Epstein-Barr Virus positive. 
     
     
         11 . The method of  claim 2 , where the patient has >10% of all CD8+ cells positive for the respective marker. 
     
     
         12 . The method of  claim 3 , where the patient has >10% of all CD8+ cells positive for the respective marker. 
     
     
         13 . The method of  claim 4 , where the patient has >10% of all CD8+ cells positive for the respective marker. 
     
     
         14 . The method of  claim 1 , where the apparatus is a commercially available, clinically approved magnetic cell separation machine. 
     
     
         15 . The method of  claim 14 , where the apparatus is a Miltenyi CliniMACS, repurposed as described herein. 
     
     
         16 . The method of  claim 1 , where the apparatus is custom-built as described herein. 
     
     
         17 . The method of  claim 1 , where the patient's peripheral blood is used to access the cells. 
     
     
         18 . The method of  claim 1 , where the patient's lymphatic system is used to access the cells.